tbuckley/cabot-search huggingface dataset:
Stress Relaxation and Composition of Hydrazone‐Crosslinked Hybrid Biopolymer‐Synthetic Hydrogels Determine Spreading and Secretory Properties of MSCs
Authors: Alexandra N. Borelli, Mark W. Young, Bruce E. Kirkpatrick, Matthew W. Jaeschke, Sarah Mellett, Seth Porter, Michael R. Blatchley, Varsha V. Rao, Balaji V. Sridhar, Kristi S. Anseth
Journal: Advanced Healthcare Materials (2022)

Abstract The extracellular matrix plays a critical role in mechanosensing and thereby influences the secretory properties of bone‐marrow‐derived mesenchymal stem/stromal cells (MSCs). As a result, interest has grown in the development of biomaterials with tunable properties for the expansion and delivery of MSCs that are used in cell‐based therapies. Herein, stress‐relaxing hydrogels are synthesized as hybrid networks containing both biopolymer and synthetic macromer components. Hyaluronic acid is functionalized with either aldehyde or hydrazide groups to form covalent adaptable hydrazone networks, which are stabilized by poly(ethylene glycol) functionalized with bicyclononyne and heterobifunctional small molecule crosslinkers containing azide and benzaldehyde moieties. Tuning the composition of these gels allows for controlled variation in the characteristic timescale for stress relaxation and the amount of stress relaxed. Over this compositional space, MSCs are observed to spread in formulations with higher degrees of adaptability, with aspect ratios of 1.60 ± 0.18, and YAP nuclear:cytoplasm ratios of 6.5 ± 1.3. Finally, a maximum MSC pericellular protein thickness of 1.45 ± 0.38 µm occurred in highly stress‐relaxing gels, compared to 1.05 ± 0.25 µm in non‐adaptable controls. Collectively, this study contributes a new understanding of the role of compositionally defined stress relaxation on MSCs mechanosensing and secretion.
Correction: Bike handlebar grip in the rectum: minimally invasive endoscopic management
Authors: Danilo Paduano, Francesco Auriemma, Mario Bianchetti, Alessandro Repici, Benedetto Mangiavillano
Journal: Endoscopy (2022)

Correction to: Bike handlebar grip in the rectum: minimally invasive endoscopic managementEndoscopy 2022; 54(02): E42-E43DOI: 10.1055/a-1362-9026
Predictive Value of Acute Neuroplastic Response to rTMS in Treatment Outcome in Depression: A Concurrent TMS-fMRI Trial
Authors: Ruiyang Ge, Afifa Humaira, Elizabeth Gregory, Golnoush Alamian, Erin L. MacMillan, Laura Barlow, Rebecca Todd, Sean Nestor, Sophia Frangou, Fidel Vila-Rodriguez
Journal: American Journal of Psychiatry (2022)

Objective: The study objective was to investigate the predictive value of functional connectivity changes induced by acute repetitive transcranial magnetic stimulation (rTMS) for clinical response in treatment-resistant depression. Methods: Cross-sectional changes in functional connectivity induced by a single concurrent rTMS-fMRI session were assessed in 38 outpatients with treatment-resistant depression (26 of them female; mean age, 41.87 years) who subsequently underwent a 4-week course of rTMS. rTMS was delivered at 1 Hz over the right dorsolateral prefrontal cortex. Acute rTMS-induced functional connectivity changes were computed and subjected to connectome-based predictive modeling to test their association with changes in score on the Montgomery-Åsberg Depression Rating Scale (MADRS) after rTMS treatment. Results: TMS-fMRI induced widespread, acute, and transient alterations in functional connectivity. The rTMS-induced connectivity changes predicted about 30% of the variance of improvement in the MADRS score. The most robust predictive associations involved connections between prefrontal regions and motor, parietal, and insular cortices and between bilateral regions of the thalamus. Conclusions: Acute rTMS-induced connectivity changes in patients with treatment-resistant depression may index macro-level neuroplasticity, relevant to interindividual variability in rTMS treatment response. Large-scale network phenomena occurring during rTMS might be used to inform prospective clinical trials.
Activity and Resistance of a Brain-Permeable Paradox Breaker BRAF Inhibitor in Melanoma Brain Metastasis
Authors: Ester Bonfill-Teixidor, Raffaella Iurlaro, Cornelia Handl, Jürgen Wichmann, Alexandra Arias, Isabel Cuartas, Jasmin Emmenegger, Andrea Romagnani, Luca Mangano, Thomas Lorber, Marco Berrera, Christina Godfried Sie, Fabian Köchl, Jan Eckmann, Romi Feddersen, Martin Kornacker, Gabriel Schnetzler, Marta Cicuendez, Esteban Cordero, Thomaz E. Topczewski, Abel Ferres-Pijoan, Josep González, Francisco Martínez-Ricarte, Eva Muñoz-Couselo, Josep Tabernero, James R. Bischoff, Piergiorgio Pettazzoni, Joan Seoane
Journal: Cancer Research (2022)

Abstract The therapeutic benefit of approved BRAF and MEK inhibitors (BRAFi/MEKi) in patients with brain metastatic BRAF V600E/K–mutated melanoma is limited and transient. Resistance largely occurs through the restoration of MAPK signaling via paradoxical BRAF activation, highlighting the need for more effective therapeutic options. Aiming to address this clinical challenge, we characterized the activity of a potent, brain-penetrant paradox breaker BRAFi (compound 1a, C1a) as first-line therapy and following progression upon treatment with approved BRAFi and BRAFi/MEKi therapies. C1a activity was evaluated in vitro and in vivo in melanoma cell lines and patient-derived models of BRAF V600E–mutant melanoma brain metastases following relapse after treatment with BRAFi/MEKi. C1a showed superior efficacy compared with approved BRAFi in both subcutaneous and brain metastatic models. Importantly, C1a manifested potent and prolonged antitumor activity even in models that progressed on BRAFi/MEKi treatment. Analysis of mechanisms of resistance to C1a revealed MAPK reactivation under drug treatment as the predominant resistance-driving event in both subcutaneous and intracranial tumors. Specifically, BRAF kinase domain duplication was identified as a frequently occurring driver of resistance to C1a. Combination therapies of C1a and anti–PD-1 antibody proved to significantly reduce disease recurrence. Collectively, these preclinical studies validate the outstanding antitumor activity of C1a in brain metastasis, support clinical investigation of this agent in patients pretreated with BRAFi/MEKi, unveil genetic drivers of tumor escape from C1a, and identify a combinatorial treatment that achieves long-lasting responses. Significance: A brain-penetrant BRAF inhibitor demonstrates potent activity in brain metastatic melanoma, even upon relapse following standard BRAF inhibitor therapy, supporting further investigation into its clinical utility.
Prevalence of Germline Findings Among Tumors From Cancer Types Lacking Hereditary Testing Guidelines
Authors: Timothy A. Yap, Arya Ashok, Jessica Stoll, Elizabeth Mauer, Vanessa M. Nepomuceno, Kimberly L. Blackwell, Judy E. Garber, Funda Meric-Bernstam
Journal: JAMA Network Open (2022)

Germline testing guidelines are suggested for specific disease types or a family history of cancer, yet alterations are found in cancer types in which germline testing is not routinely indicated. The clinical role of identifying germline variants in these populations is valuable to patients and their at-risk relatives.
Rapid Antigen Tests for SARS-CoV-2—Reply
Authors: Joshua S. Gans, Avi Goldfarb, Laura Rosella
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Improving Patient Advocacy in NCI Scientific Steering Committees and Task Forces
Authors: Rick Bangs, Jean M Lynn, Evelyn Obot, Sherill Osborne, Kim Norris
Journal: JNCI Journal of the National Cancer Institute (2022)

This commentary discusses improving research advocacy as part of National Cancer Institute (NCI) clinical trial activities in scientific steering committees and task forces between 2016 and 2020. Before 2016, the focus of patient advocate input on clinical trial concept evaluation was assessing accrual feasibility. By leveraging informal benchmarking and an outside-in perspective, the NCI patient advocate steering committee, comprised of NCI scientific steering committee and task force advocates, has recalibrated research advocacy within and across its clinical trial concepts. Additionally, by focusing on research advocacy fundamentals, the NCI patient advocate steering committee clarified the scope of the research advocate roles, focused its mission, defined and developed competencies, measured engagement, and created collateral and processes that support better interactions and greater value generation. Continuous improvement in the collateral and the underlying approaches, along with calibrating their application and monitoring results, will be necessary to keep pace with the science and further enhance the value of cancer clinical trial research advocacy. The road ahead should build on these fundamentals and include increased emphasis on diversity, equity, and inclusion in clinical trial and research advocacy participants and the supporting infrastructure.
War against <i>NRAS</i>-Mutant Melanoma Using Targeted Therapies Remains Challenging
Authors: Stergios J. Moschos
Journal: Clinical Cancer Research (2022)

Summary In the search for targeting MAPK plus other pathways in NRAS-mutant melanoma, a phase Ib/II trial tested binimetinib plus ribociclib in metastatic melanoma. The response rate in the phase II trial was 19.5%, and the median progression-free survival was 3.7 months. See related article by Schuler et al., p. 3002
Neutralization of the SARS-CoV-2 Deltacron and BA.3 Variants
Authors: John P Evans, Panke Qu, Cong Zeng, Yi-Min Zheng, Claire Carlin, Joseph S Bednash, Gerard Lozanski, Rama K Mallampalli, Linda J Saif, Eugene M Oltz, Peter J Mohler, Richard J Gumina, Shan-Lu Liu
Journal: New England Journal of Medicine (2022)
Mutation Load in Sunflower Inversions Is Negatively Correlated with Inversion Heterozygosity
Authors: Kaichi Huang, Kate L. Ostevik, Cassandra Elphinstone, Marco Todesco, Natalia Bercovich, Gregory L. Owens, Loren H. Rieseberg
Journal: Molecular Biology and Evolution (2022)

Abstract Recombination is critical both for accelerating adaptation and purging deleterious mutations. Chromosomal inversions can act as recombination modifiers that suppress local recombination in heterozygotes and thus, under some conditions, are predicted to accumulate such mutations. In this study, we investigated patterns of recombination, transposable element abundance, and coding sequence evolution across the genomes of 1,445 individuals from three sunflower species, as well as within nine inversions segregating within species. We also analyzed the effects of inversion genotypes on 87 phenotypic traits to test for overdominance. We found significant negative correlations of long terminal repeat retrotransposon abundance and deleterious mutations with recombination rates across the genome in all three species. However, we failed to detect an increase in these features in the inversions, except for a modest increase in the proportion of stop codon mutations in several very large or rare inversions. Consistent with this finding, there was little evidence of overdominance of inversions in phenotypes that may relate to fitness. On the other hand, significantly greater load was observed for inversions in populations polymorphic for a given inversion compared to populations monomorphic for one of the arrangements, suggesting that the local state of inversion polymorphism affects deleterious load. These seemingly contradictory results can be explained by the low frequency of inversion heterozygotes in wild sunflower populations, apparently due to divergent selection and associated geographic structure. Inversions contributing to local adaptation represent ideal recombination modifiers, acting to facilitate adaptive divergence with gene flow, while largely escaping the accumulation of deleterious mutations.
Regulatory analysis of single cell multiome gene expression and chromatin accessibility data with scREG
Authors: Zhana Duren, Fengge Chang, Fnu Naqing, Jingxue Xin, Qiao Liu, Wing Hung Wong
Journal: Genome biology (2022)

Abstract Technological development has enabled the profiling of gene expression and chromatin accessibility from the same cell. We develop scREG, a dimension reduction methodology, based on the concept of cis -regulatory potential, for single cell multiome data. This concept is further used for the construction of subpopulation-specific cis -regulatory networks. The capability of inferring useful regulatory network is demonstrated by the two-fold increment on network inference accuracy compared to the Pearson correlation-based method and the 27-fold enrichment of GWAS variants for inflammatory bowel disease in the cis -regulatory elements. The R package scREG provides comprehensive functions for single cell multiome data analysis.
Outcomes following venetoclax‐based treatment in therapy‐related myeloid neoplasms
Authors: Mithun Vinod Shah, Rakchha Chhetri, Ruchita Dholakia, Chung H. Kok, Naseema Gangat, Hassan B. Alkhateeb, Aref Al‐Kali, Mrinal M. Patnaik, Anmol Baranwal, Patricia T. Greipp, Rong He, Kebede H. Begna, Ing Soo Tiong, Andrew H. Wei, Devendra Hiwase
Journal: American Journal of Hematology (2022)

Therapy-related myeloid neoplasms (t-MN) are aggressive malignancies in need of effective therapies. The BCL-2 inhibitor venetoclax represents a paradigm shift in the treatment of acute myeloid leukemia. However, the effectiveness of venetoclax has not been studied in a large cohort of t-MN. We retrospectively analyzed 378 t-MN patients, of which 96 (25.4%, 47 therapy-related acute myeloid leukemia, 1 therapy-related chronic myelomonocytic leukemia, 48 therapy-related myelodysplastic syndrome) received venetoclax. Median interval from t-MN to venetoclax initiation was 2.9 (Interquartile range [IQR] 0.7-12) months, and patients received a median of 3 (IQR 1-4) cycles. The composite complete remission (CRc) rate, median progression-free survival (PFS), and overall survival (OS) were 39.1%, 4.9 months, and 7 months, respectively. The upfront use of venetoclax and achieving CRc were associated with improved survival, whereas the presence of Chromosome 7 abnormalities was associated with an inferior survival. Neither the TP53-status nor the percent bone marrow blast predicted the likelihood of CRc or survival. Paired genetic analysis performed at venetoclax initiation and failure did not show the evidence of the selection of the TP53-mutated clone. In a propensity-matched analysis, the use of venetoclax-based regimen as the first-line therapy was associated with a superior survival compared to hypomethylating agent (HMA)-based first-line therapy (9.4 vs. 6.1 months, p = .01). We conclude that the upfront use of venetoclax with HMA improved survival, though PFS and OS remain poor. As the phenotype at diagnosis or the percent blasts did not predict outcomes, venetoclax should be studied in all t-MN phenotypes.
Distinct phenotypic states and spatial distribution of CD8+ T cell clonotypes in human brain metastases
Authors: Lisa J Sudmeier, Kimberly B Hoang, Edjah K Nduom, Andreas Wieland, Stewart G Neill, Matthew J Schniederjan, Suresh S Ramalingam, Jeffrey J Olson, Rafi Ahmed, William H Hudson
Journal: Cell Reports Medicine (2022)
Moderate Hypothermia vs Normothermia and 30-Day Mortality in Patients With Cardiogenic Shock Receiving Venoarterial ECMO—Reply
Authors: Bruno Levy, Alain Combes, Nicolas Girerd
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract IA020: Dynamics of response and resistance to cancer therapy
Authors: Ivana Bozic
Journal: Cancer Research (2022)

Abstract Despite the effectiveness of many cancer therapies in reducing tumor burden for significant amounts of time in a subset of patients, primary and acquired resistance to treatment remain one of the biggest challenges in the effort to cure cancer. Successful management, or prevention, of resistance requires deciphering the mechanisms by which it arises, and in particular whether it stems from pre-existing cell populations or arises de novo during therapy. Using evolutionary principles and mathematical techniques together with patient data, we aim to develop a precise mathematical understanding of the dynamics of response and resistance to various cancer therapies, including targeted therapies and immunotherapy. Our work shows that therapies that maximize the killing rate of cancer cells may not be optimal, and that instead the parameters determining the fraction of resistant cells and their growth rate have a larger effect on the long-term control of cancer. Citation Format: Ivana Bozic. Dynamics of response and resistance to cancer therapy [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr IA020.
Disrupting mechanotransduction decreases fibrosis and contracture in split-thickness skin grafting
Authors: Kellen Chen, Dominic Henn, Michael Januszyk, Janos A. Barrera, Chikage Noishiki, Clark A. Bonham, Michelle Griffin, Ruth Tevlin, Theresa Carlomagno, Tara Shannon, Tobias Fehlmann, Artem A. Trotsyuk, Jagannath Padmanabhan, Dharshan Sivaraj, David P. Perrault, Alsu I. Zamaleeva, Chyna J. Mays, Autumn H. Greco, Sun Hyung Kwon, Melissa C. Leeolou, Savana L. Huskins, Sydney R. Steele, Katharina S. Fischer, Hudson C. Kussie, Smiti Mittal, Alana M. Mermin-Bunnell, Nestor M. Diaz Deleon, Christopher Lavin, Andreas Keller, Michael T. Longaker, Geoffrey C. Gurtner
Journal: Science Translational Medicine (2022)

Burns and other traumatic injuries represent a substantial biomedical burden. The current standard of care for deep injuries is autologous split-thickness skin grafting (STSG), which frequently results in contractures, abnormal pigmentation, and loss of biomechanical function. Currently, there are no effective therapies that can prevent fibrosis and contracture after STSG. Here, we have developed a clinically relevant porcine model of STSG and comprehensively characterized porcine cell populations involved in healing with single-cell resolution. We identified an up-regulation of proinflammatory and mechanotransduction signaling pathways in standard STSGs. Blocking mechanotransduction with a small-molecule focal adhesion kinase (FAK) inhibitor promoted healing, reduced contracture, mitigated scar formation, restored collagen architecture, and ultimately improved graft biomechanical properties. Acute mechanotransduction blockade up-regulated myeloid CXCL10-mediated anti-inflammation with decreased CXCL14-mediated myeloid and fibroblast recruitment. At later time points, mechanical signaling shifted fibroblasts toward profibrotic differentiation fates, and disruption of mechanotransduction modulated mesenchymal fibroblast differentiation states to block those responses, instead driving fibroblasts toward proregenerative, adipogenic states similar to unwounded skin. We then confirmed these two diverging fibroblast transcriptional trajectories in human skin, human scar, and a three-dimensional organotypic model of human skin. Together, pharmacological blockade of mechanotransduction markedly improved large animal healing after STSG by promoting both early, anti-inflammatory and late, regenerative transcriptional programs, resulting in healed tissue similar to unwounded skin. FAK inhibition could therefore supplement the current standard of care for traumatic and burn injuries.
Controlled release of low-molecular weight, polymer-free corticosteroid coatings suppresses fibrotic encapsulation of implanted medical devices
Authors: Pardis Pakshir, Fereshteh Younesi, Kelli-Anne Wootton, Kyle Battiston, Greg Whitton, Bernadette Ilagan, Dimitra Louka, Matthew Statham, Gillian Mackey, Adam Daley, Ian Parrag, Wendy Naimark, Boris Hinz
Journal: Biomaterials (2022)
Patients with transplantation have reduced mortality in bacteraemia: Analysis of data from a randomised trial
Authors: Fergus Hamilton, Rebecca Evans, Peter Ghazal, Alasdair MacGowan
Journal: Journal of Infection (2022)

Infection remains a major complication of organ transplantation. Paradoxically, epidemiological studies suggest better survival from serious infection. We analysed the relationship between organ transplantation and short -term mortality of patients with bloodstream infection.
Abstract B017: Homotypic cell-cell fusion in TNBC cells downregulates cancer testis antigen MAGEC2 and increases therapeutic sensitivity to paclitaxel and doxorubicin
Authors: Andrea Gardner, Lan Zheng, Kennedy Howland, Chisom Iloegbunam, Patrik Barrera, Carolina De Santiago, Amy Brock
Journal: Cancer Research (2022)

Abstract This abstract is being presented as a short talk in the scientific program. A full abstract is available in the Proffered Abstracts section (PR007) of the Conference Proceedings. Citation Format: Andrea Gardner, Lan Zheng, Kennedy Howland, Chisom Iloegbunam, Patrik Barrera, Carolina De Santiago, Amy Brock. Homotypic cell-cell fusion in TNBC cells downregulates cancer testis antigen MAGEC2 and increases therapeutic sensitivity to paclitaxel and doxorubicin [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr B017.